This study investigated the utility of PIVA during CPR in a rat model of asphyxial CA. Our results show that PIVA was able to detect an increase in venous return with subsequent increase in etCO2 followed by ROSC. Across all experiments, PIVA consistently exhibited sequential peaks in the tail vein, followed by the femoral vein and central venous site. Notably, all PIVA peaks occurred prior to the rise in etCO2 levels. These results suggest that a decrease in PIVA signal indicates achievement of a critical threshold of blood flow during CPR and might predict the occurrence of ROSC.

To the best of our knowledge, we are the first group to measure peripheral venous pressure and analyze its components during CPR. Previous studies described a retrograde venous flow during compressions, but only with the consequence that this palpable pulsation could be misleading for pulse checks or arterial cannulations [10, 11, 28]. This backflow phenomenon is reflected in our study with an early increase of venous amplitudes in all peripheral catheters, seen by increasing pressure amplitudes and calculated by PIVA values. However, as pressure amplitudes are decreasing during the course of CPR, PIVA detects a decrease of retrograde venous flow, when venous return increases and hemodynamics improve. These findings are also based on the fluid dynamic principles: If a pulsation travels toward a closed end of a tube, the amplitude increases due to reflection. Conversely, if the pulsation decreases and travels toward the open end, the amplitude decreases as there is no reflection.

Particularly important at this point is the CVP pulsation, previously defined as CVP-A, resulting in PIVA peaks short before ROSC: In a recent study, we were able to show that a high CVP-A during CPR was associated with a higher successful defibrillation rate, which underlines the notion that PIVA peaks could reflect venous return and a critical threshold of flow that improves the chances for ROSC and improved outcomes [17]. An important common feature of this investigation and the present study is the significance of the amplitude as opposed to the average value of the venous pressure. Just as the CVP as a static measurement has little significance for the outcome compared to the CVP-A, the significance of the peripheral venous pressure is hidden in the close observation of the peripheral venous pressure curve by PIVA and, thus, offers a promising dynamic parameter.

Furthermore, it is of great importance that this study, like the CVP-A study, describes changes in venous amplitudes significantly earlier than etCO2. While increased venous return and increased CO2 delivery to the lungs occur simultaneously after ROSC, there are physiologic reason for the delay in detecting ROSC by etCO2. First, the CO2 washout from the tissue after poor perfusion takes time [29]. Additionally, CO2 is delayed by circulatory factors due to the distance the blood must travel before reaching the lungs [30]. The release of CO2 by the lungs is further impaired due to uneven alveolar ventilation and a perfusion mismatch, before the CO2 can be detected by a capnometer [29].

One crucial aspect is that etCO2 measurements can only be reliably obtained from patients who are intubated and ventilated using equipment capable of CO2 monitoring. Conversely, PIVA holds the potential for widespread clinical utilization as it relies on the simple procedure of peripheral intravenous cannulation, which is highly recommended for all patients undergoing CPR [1].

Another indicator for the significance of PIVA, as the earliest indicator of a critical threshold of blood flow before ROSC, are the values of other hemodynamic parameters at the time point of the PIVA peak (Table 2). At this timepoint exhibits none of the values, that could be predictive for ROSC, provide clinical forecasting values in context with the values over time (Table 1).

With further development of this parameter into a device with immediate feedback, a novel instrument could offer significant benefits by providing immediate insights into venous return and the quality of CPR, which is critical for guiding medical personnel during resuscitation.

The results of this study, however, need to be evaluated within their natural constraints. While real-time analysis has the potential to improve CPR, our study was a retrospective analysis, which could only identify the PIVA peak and subsequent fall in retrospect. Furthermore, the sample size was small in this feasibility study, and more studies with different CA modalities will be needed to confirm our findings. In particular, we only examined one CA etiology. While asphyxial CA leads to heart failure with consecutive venous fluid overload, PIVA signals after sudden CA with, e.g., ventricular fibrillation could detect different venous waveforms during CPR. Furthermore, the etCO2 threshold needs to vary depending on the etiology of cardiac arrest to fully realize the potential of PIVA, as different arrest mechanisms, such as asphyxial versus fibrillatory, result in significantly different etCO2 dynamics. Another limitation is the absence of a control group without ROSC. This limitation is caused by the rodent asphyxial cardiac arrest model itself, since omitting or delaying catecholamines is not a safe method of avoiding ROSC, and there is evidence that ROSC can also occur without epinephrine in this model [31, 32]. As a next step, we will not only test PIVA in different CA models, but we are also preparing a clinical study to test PIVA during CPR in the field.